2y1w

Structural highlights

Function

CARM1_HUMAN Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs.^{[1] [2]}

See Also

• Histone methyltransferase 3D structures

References

1. ↑ Miao F, Li S, Chavez V, Lanting L, Natarajan R. Coactivator-associated arginine methyltransferase-1 enhances nuclear factor-kappaB-mediated gene transcription through methylation of histone H3 at arginine 17. Mol Endocrinol. 2006 Jul;20(7):1562-73. Epub 2006 Feb 23. PMID:16497732 doi:me.2005-0365
2. ↑ Lakowski TM, Frankel A. Kinetic analysis of human protein arginine N-methyltransferase 2: formation of monomethyl- and asymmetric dimethyl-arginine residues on histone H4. Biochem J. 2009 Jun 26;421(2):253-61. doi: 10.1042/BJ20090268. PMID:19405910 doi:10.1042/BJ20090268
3. ↑ Sack JS, Thieffine S, Bandiera T, Fasolini M, Duke GJ, Jayaraman L, Kish KF, Klei HE, Purandare AV, Rosettani P, Troiani S, Xie D, Bertrand JA. Structural basis for CARM1 inhibition by indole and pyrazole inhibitors. Biochem J. 2011 Jun 1;436(2):331-9. PMID:21410432 doi:10.1042/BJ20102161